Objective To examine the effects of prenatal exposure to persistent organic pollutants (POPs) on rapid growth in the first 6 months of life and overweight at 14 months of age. Design and Methods In a Spanish birth cohort study, the POPs dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs - congeners 153, 138, 180) were measured in maternal serum collected in the first trimester of pregnancy during 2003-2008. Rapid growth was defined as a z-score weight gain >0.67 SD between 6 months of age and birth. Overweight at 14 months was defined as a BMI z-score ≥85th percentile. Generalized linear models examined the association between POPs and rapid growth (N = 1285) and overweight (N = 1198). Results The analysis population included 24% rapid growers and 30% overweight infants. DDE and HCB were positively associated with rapid growth and with overweight. There was some indication that infant sex and exclusive breastfeeding duration may modify the effects of DDE, and that maternal prepregnancy BMI status may influence the effects of HCB. PCBs were not related to postnatal growth. Conclusion Prenatal exposure to DDE and HCB may be associated with early postnatal growth. Further research is needed to evaluate the persistence of these associations at older ages.